Recent research suggests that the antioxidant resveratrol, which naturally occurs in grape skins, can weaken pancreatic cancer cells and increase their vulnerability to chemotherapy.
“Resveratrol seems to have a therapeutic gain by making tumor cells more sensitive to radiation and making normal tissue less sensitive,” said lead researcher Paul Okunieff, chief of radiation oncology at the University of Rochester Medical Center.
In a study published in the journal Advances in Experimental Medicine and Biology,Okunieff and colleagues treated a group of pancreatic cancer cells with 50 mg of resveratrol, then iodized them to simulate the action of chemotherapy. Another group of cancer cells was iodized without undergoing any resveratrol treatment.
Pancreatic cancer has long been known to be particularly resistant to chemotherapy. The researchers discovered that because the pancreas is continually producing digestive enzymes and pumping them into the duodenum, these enzymes actually flush away chemotherapy chemicals before they can have much impact.
But in pancreatic cancer cells that had been treated with resveratrol, the cell membrane proteins responsible for this flushing had their functioning hampered. In addition to becoming more sensitive to chemotherapy, the cells also became more likely to undergo programmed death (apoptosis) due to the increased production of reactive oxygen species.
While the reason for the decreased pumping action was not clear, it may have been a side effect of yet a third observed effect of resveratrol treatment: The mitochondria of the cancer cells was damaged, with its membranes depolarized. Because mitochondria are the energy source of the cell, damaged mitochondria hampers the cell’s general ability to function, including its ability to flush out chemotherapy drugs.
As a naturally occurring ingredient of red wine, resveratrol has drawn much attention from researchers investigating whether it might be responsible for wine’s well-documented health benefits. Like all antioxidants, resveratrol is known to remove free radicals from the blood. Free radicals are known to be linked with cancer, inflammation related to cardiovascular disease, and the effects of aging.
But scientists are also hard at work uncovering resveratrol’s more specific effects. Numerous studies have demonstrated that the chemical can extend the lifespan of simple organisms such as worms and yeast, and even complex animals like fish. In one 2003 study, short-lived fish dosed with resveratrol lived more than 50 percent longer than fish not treated with the antioxidant. In addition, these fish had better swimming and learning ability at the end of their lives than the control fish did.
Other studies have shown that resveratrol protects plants from bacterial or fungal infection and makes HIV more susceptible to certain antiviral drugs. In cells infected with the influenza virus, resveratrol treatment reduced the virus’ ability to reproduce by 90 percent over a period of 24 hours.
Resveratrol has also been shown to improve treadmill endurance in mice, and even to neutralize the negative effects of a high-fat diet. Mice fed a high-fat diet supplemented with 22 mg/kg of resveratrol had a 30 percent lower chance of dying when compared with mice eating only an unsupplemented high fat diet. This was approximately the same risk of death as mice eating a normal, non-high-fat diet.
Finally, a number of studies have suggested that the antioxidant has anti-cancer benefits, from preventing the development of skin cancer in mice exposed to ultraviolet radiation to reducing the risk of esophageal or colorectal tumors in mice and rats exposed to carcinogens. It has also been shown to induce apoptosis in human fat cells under certain specific circumstances.
“Antioxidant research is very active and very seductive right now,” Okunieff said. “The challenge lies in finding the right concentration and how it works inside the cell.”
The highest concentrations of resveratrol are found in grape skins. Peanuts contain about half as much resveratrol as grapes, while blueberries and bilberries contain only about 10 percent as much.
While the resveratrol content of wine varies widely depending on the variety of grape, when and where it was grown, and how long it was fermented, the high level tends to be 30 mg per ml. This is lower than the dose used in the current study. But Okunieff said that higher doses should be safe as long as they are taken under a doctor’s supervision.
“While additional studies are needed, this research indicated that resveratrol has a promising future as part of the treatment for cancer,” he said.
Approximately 33,000 new cases of pancreatic cancer are diagnosed in the United States every year. Patients have a very low rate of survival, in part due to the disease’s resistance to chemotherapy.